When we launched in June 2007, we wanted to support the stem cell field and the interested public by providing freely available content. Stem cell research was then – and is still – exciting and expanding. It requires highly varied experts to think and work together, and it requires the support and understanding of non-scientists. We believe we have been successful in creating a venue that highlights and explores the many facets and implications of stem cell science. It is now time for us to move on to fresh publishing challenges.

We have been helped by many contributors and experts who have generously given their time and insight. We give a heartfelt thanks to everyone who wrote articles or gave interviews, advice, and words of encouragement.

NRSC and this blog will continue to remain online as an archive. Nature and its sister titles remain committed, as ever, to publishing new research and news about stem cells.

Monya Baker, Editor

Natalie DeWitt, Editor at Large

]]>/theniche/2009/10/goodbye_from_nature_reports_st.html/feed0Stanford conference: stem cells, the new NIH, and delimiting embryo research/theniche/2009/10/stanford_conference_stem_cells.html
/theniche/2009/10/stanford_conference_stem_cells.html#commentsFri, 09 Oct 2009 02:17:04 +0000mbaker/theniche/2009/10/stanford-conference-stem-cells-the-new-nih-and-delimiting-embryo-research.htmlRead more]]>Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over the next few blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

The people who will assess which human embryonic stem cell lines should be eligible for U.S. federal funding will meet next week, said Story Landis, head of the Stem Cell Task Force at the U.S. National Institutes of Health. In March this year, President Barack Obama charged the NIH with crafting policy to allow the funding of responsible embryonic stem cell research. In July, the NIH declared that this would include cell lines created from embryos made for reproductive purposes and donated without financial inducements and with proper informed consent. Determining proper informed consent is a bit of a minefield, particularly for embryos donated in the 1990s, before much of the debate and consensus-building around the issue occurred. See Stem cell vetting raises concerns, confusion

In July, the NIH announced that it would assemble a working group to decide which cell lines closely conform with current thinking on informed consent criteria and to establish a central registry of cell lines deemed eligible for federal funding. “This is incredibly fast work for the federal government,” Landis said.

The NIH also established a registry under President George W. Bush, but that was restricted to cell lines created before 9 August 2001, the date of Bush’s speech describing the policy. For the updated NIH registry, new cell lines can be added as long as they meet the NIH’s criteria. Moreover, Landis said, the guidelines will be reviewed periodically. That would potentially allow future inclusion of embryos created by nuclear transfer (cloning) or from unfertilized eggs, assuming adequate public support and a clear scientific case for the use of these cells. (A cell line’s inclusion in the registry, Landis said, is expected to be permanent.) Stanford’s Irving Weissman, who believes that lines from unfertilized eggs and cloned early embryos should be considered now, asked about the role of politics and ideology in decisions of setting scientific policy. Landis replied that “no one was happy with the guidelines”, referring to the tension between those who would restrict which lines could be funded and those who would expand eligibility. She said that the guidelines had not been drafted “in a vacuum”.

Landis also discussed Congressional legislation governing research on embryos. The Dickey-Wicker Amendment, which prohibits the use of appropriated funds for the creation of human embryos intended for research purposes, became law in 1996 and must be renewed regularly. Landis said that the scope of the legislation has expanded since its first implementation; she seemed to think such expansion would continue and that this situation should be more closely monitored by researchers.

Don Reed, a long opponent of the legislation, suggested reinterpreting it so that the word ‘embryo’ refers only to implanted embryos rather than to fertilized eggs in laboratories, and Landis indicated that she favoured a more direct discussion of what research could (and should) be funded.

Research by Stanford’s Renee Reijo Pera gave a clear example of the kind of work that the federal government cannot support. Using a very high-tech system, she and her colleagues tracked the development of human fertilized eggs. This led to a better understanding of what goes wrong when a zygote fails to develop into a ball-shaped embryo and what markers indicate which very early-stage embryos will form blastocysts. The application of this work, she said, is not only that couples receiving fertility treatment would need to make and implant fewer embryos, but also that embryos could be transplanted at an earlier stage. (I’m being a little vague here because the results are not yet published.) This, in turn, could mean that fewer in vitro fertilization procedures would result in multiple pregnancies (carrying twins, triplets, quadruplets and so on), a situation that increases risks for both mother and offspring and that requires painful decisions of whether to selectively terminate one or more foetuses to increase the chances of delivering a healthy baby. “All you have to see is one couple who has to do a foetal reduction, and you think you’ve entered hell,” Pera said.

]]>/theniche/2009/10/stanford_conference_stem_cells.html/feed0Stanford conference: patient-heroes of clinical research/theniche/2009/10/stanford_conference_patienther.html
/theniche/2009/10/stanford_conference_patienther.html#commentsFri, 09 Oct 2009 02:15:51 +0000mbaker/theniche/2009/10/stanford-conference-patient-heroes-of-clinical-research.htmlRead more]]>“When you think you have a policy, you’re too late.” That’s the opinion of Pearl O’Rourke, who directs human research affairs at Partner Healthcare Systems She was referring to the pace of research in the stem cell field and the need to fashion policies to protect subjects. Embryonic stem cell research oversight committees are becoming too much of a catchall, she worries.

Insoo Hyun, of Case Western Reserve University, said that the ethical considerations for stem cell–based clinical trials were similar to those for other experimental procedures but with the “heat” turned up — patients are more desperate, procedures are riskier, snake-oil salesmen more of a factor and slots in research trials are fewer. Outside clinical trials, perhaps some of the thinking developed for assessing new surgical techniques could be useful. Organ transplants, after all, did not go through clinical trials. Thomas Okarma, president and CEO of Geron, which is developing an embryonic stem cell product for spinal cord injury, described how he thought the cells might work (one mechanism is the secretion of various health factors, which could have implications for stroke and Alzheimer’s disease). At the same time, he said his company is committed to “maintain[ing] a conservative risk-benefit calculus”, which basically means only trying the riskiest therapies in very ill patients with very few other options, thus reducing the potential to harm patients.

Stanford University’s Hank Greely shared a few thoughts to guide this kind of analysis. Regulators demand that research be safe, but the very uncertainty makes this impossible, he said. That, in a sense, makes those who participate in Phase I trials heroes. No one can be certain what will happen when some new therapy or procedure is tried in humans. And consent is particularly important when the risk is high, he said, indicating that risky procedures should be tested in adult patients before children, even if a procedure is more likely to work in a younger population.

Finally, he lamented the fact that because conversations between regulatory authorities and clinical trial sponsors are confidential, crucial risk-reducing, therapy-speeding knowledge does not spread freely. He called on those involved to reveal the thinking behind regulatory decisions.

Editor’s note: Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over three blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

]]>/theniche/2009/10/stanford_conference_patienther.html/feed0Stanford conference: Geron’s 345 patents and reasons for stem cell intellectual property/theniche/2009/10/stanford_conference_gerons_345.html
/theniche/2009/10/stanford_conference_gerons_345.html#commentsFri, 09 Oct 2009 02:13:51 +0000mbaker/theniche/2009/10/stanford-conference-geron%e2%80%99s-345-patents-and-reasons-for-stem-cell-intellectual-property.htmlRead more]]>Perhaps more confusing than making and using stem cells are the intellectual property rules governing such use. In addition to the licenses his company has attained from the Wisconsin Alumni Research Foundation, David Earp, patent counsel for Geron, said that his company had filed more than 300 patents covering a variety of areas: undifferentiated cells; differentiated cells; methods to scale, differentiate and process cells; and ways to grow cells without blood products and feeder layers.

Esther Kepplinger of the law firm Wilson Sonsini Goodrich & Rosati and Robin Feldman of the University of California Hastings College of the Law provided a stem cell–focused tutorial on what criteria a valid patent must establish and what areas a patent can cover. For instance, a patent can cover the cells themselves, the method of producing the cells or the use of cells in therapy or diagnosis.

Kepplinger, who oversaw the assessment of patents at the U.S. Patent and Trademark Office before joining the law firm, said that from what she’s seen, the patent office is rejecting more patents and claims have been getting narrower. She also said that because stem cell patents are likely to be of high public interest, they can receive extra scrutiny. Finally, she defended the existence of patents themselves: without them, she said, companies would not make the necessary investments to develop new products.

Aurora Plomer, of the University of Sheffield Law School, described what she considers a sort of drift of the European Patent Office’s directive declaring that uses of human embryos for industrial or commercial purposes are not patentable. The intention of the directive was to prevent fertility clinics from turning embryos into commodities. The interpretation of the directive to cover embryonic stem cells, products made from embryonic stem cells and products made with research using embryonic stem cells is highly flawed, she says.

Editor’s note: Students from the law and medical schools at Stanford University brought together an impressive group of world-class experts last week to discuss stem cell policy. I’ll describe some (very select) highlights over three blogs. Check the site for the Stanford Journal of Law Science & Policy over the next few weeks for powerpoints presentations and audiorecordings.

]]>/theniche/2009/10/stanford_conference_gerons_345.html/feed0A small molecule replaces Sox2, and honors baseball/theniche/2009/10/a_small_molecule_replaces_sox2.html
/theniche/2009/10/a_small_molecule_replaces_sox2.html#commentsThu, 08 Oct 2009 18:30:54 +0000mbaker/theniche/2009/10/a-small-molecule-replaces-sox2-and-honors-baseball.htmlRead more]]>The standard technique for creating make differentiated cells behave like embryonic stem cells uses viruses to insert the genes cMyc, Klf4, Oct4, and Sox2 into cells, but adding these genes to cells makes them less predictable and more likely to form tumors. Researchers have been able to reprogram neural stem cell using only Oct4, but these cells are not readily available from patient biopsies and so researchers are searching for alternate techniques. New work published in Cell Stem Cell shows that a small druglike molecule can effectively replace two of the four genes typically used to generate induced pluriptotent stem cells.

To begin their hunt for compounds that could help reprogram cells, researchers led by Kevin Eggan and Lee Rubin of the Harvard Stem Cell Institute used cultures of mouse skin cells engineered to express green fluorescent protein as a marker of pluripotency. They first screened for small molecules that allowed mouse cells to be reprogrammed without adding the gene for Sox2. When three such molecules were identified, the researchers tried again and found that one of the molecules could reprogram cells even in the absence of cMyc, a tumour-promoting gene that, while not required for reprogramming, greatly boosts reprogramming rates.

To make sure the cells were really reprogrammed, the researchers performed a series of tests, including mixing them with mouse embryos and demonstrating that they could contribute to every type of tissue in chimeric mice. They named the identified molecule RepSox for its ability to replace Sox2 and also after the Red Sox, the local baseball team. Previous studies had identified this molecule as inhibiting a pathway known as TGF-beta signaling. Careful work showed that RepSox did not work by activating the Sox2 gene in fibroblasts, as might be expected. Instead, the molecule functions in partially reprogrammed cells that accumulate in the absence of Sox2, apparently by inducing and stabilizing Nanog expression. Thus, the researchers write, the discovery of RepSox is important not only for replacing one of the reprogramming factors but for illuminating a new strategy to identifying such molecules. “There need not always be a discrete, one-to-one mapping between the functions of the reprogramming factors and their chemical replacements.”

Robert Blelloch, who studies reprogramming at the University of California San Francisco, praised the team’s strategy of only screening compounds whose mechanisms are at least partly understood. “They find a small molecule that replaces a factor, but they take it further and use it to understand the biology.”

]]>/theniche/2009/10/a_small_molecule_replaces_sox2.html/feed0Notes on a neural stem cell conference/theniche/2009/10/notes_on_a_neural_stem_cell_co.html
/theniche/2009/10/notes_on_a_neural_stem_cell_co.html#commentsTue, 06 Oct 2009 19:29:35 +0000mbaker/theniche/2009/10/notes-on-a-neural-stem-cell-conference.htmlRead more]]>Editor’s note: The stem cell world has been rich with conferences in the past week or so. I hope to have very brief notes on Cold Spring Harbor Laboratory and Stanford’s interdisciplinary program on stem cell policy over the next few days. For the recent World Stem Cell Conference in Baltimore, please check for Elie Dolgin’s posts in In the Field.

The conference report below comes from Julie Clark, a scientist at Stemgent, who had previously covered the ISSCR conference for the Niche, and volunteered again. Thanks very much to Julie! —Monya

With the possibility of cell replacement therapy on the horizon, this symposium probed how neural stem cells function in brain development and repair.

The origin of neural stem cells and building and repairing the cortex were the emphasis of the first of this two day symposium. Here are a few highlights.

Fingering zinc in cell fate

Yoshiki Sasai, MD, PhD from Kobe RIKEN discussed the identification of Zfp521, a zinc finger protein required for the transition of common ectoderm cells to a neuroectodermal fate. Sasai showed the forced up-regulation of Zfp521 causes neural differentiation and its knock down inhibits neural differentiation of embryonic stem cells.

Susan McConnell PhD from Stanford identified another zinc finger protein, Fezf2, which appears to regulate motor neuron fate. Loss of Fezf2 results in the failure of neurons to send axons to the spinal cord and development of the corpus callosum.

New sorts of neural stem cells

Arnold Kriegstein MD, PhD from UCSF wowed the crowd with videos of radial glial cell (RGC) division, showing that during cell division RGCs do not retract their axons. Once thought to be just scaffolding, radial glial cells have been shown to be NSCs/progenitors.

Derek van der Kooy, PhD from the University of Toronto showed evidence that a small population of leukemia inhibitory factor (LIF) sensitive primitive neural stem cells (NSCs) is preserved in the adult forebrain (approximately 5-10 cells in adult mice). Primitive NSCs can be activated to replace the definitive neural stem cells lost to chemical stress.

The eyes have it

Sally Temple PhD from the New York Stem Cell Institute showed that cells of the retinal pigment epithelium (RPE)collected from the sub-retinal fluid discarded after retinal surgeries can be isolated from human eye, expanded, and differentiated into a variety of cells (e.g. retinal cells, neurons, fat, chondrocytes, and bone). RPE cell biopsies would require putting needles into the sub-retinal space, a very routine procedure for retinal surgeons and can be considered as a source of patient matched progenitor cells for regenerative medicine.

Meninges push proliferation

Samuel Pleasure MD, PhD discussed the role of the meninges in cortical neurogenesis. In addition to functioning as the basement membrane for radial glia attachment, Pleasure showed that the cortical meninges also secret soluble factors (e.g. retinoic acid), influencing the transition of symmetrical to asymmetrical phase proliferation of neural stem cells crucial to the production of neurons in the underlying cortex.

Day2

The second day of the International Stem Cell Symposium: Frontiers in Neural Stem Cells had an equally impressive lineup of speakers with surprisingly passionate requests for scientific diversity and support for basic research funding. The emphases of the second day were on generating new neurons and glial cells and stem cell models of neurological disease.

Pheromones, neurons make social memories; social changes change neuron survival

Samuel Weiss PhD from the University of Calgary showed evidence of adult neurogenesis in response to pheromones resulting in the formation of social memories (e.g. recognition of offspring) in mice.

Fernando Nottebohm PhD from Rockerfeller University discussed the effects on neuron survival or killing as a result of social changes in zebra finches. Nottebohm also reflected on the changing belief of adult neurogenesis during his scientific career, spanning over 4 decades, but will be remembered most for his passionate plea advocating that governments and young scientists move toward basic science and resist the push for translational research “studies of aging are studies of boredom.”

Competition at the synapse

Fred Gage PhD from the Salk Institute showed that neural synapses are maintained through competition between new and old neurons and new neurons add complexity to pattern separation and integration. Gage further showed retrotransposons line elements creating genetic mosaics in the brain.

Astrocytes instigate synapses

Ben Barres MD, PhD from Stanford presented data from a soon to be published manuscript in Cell, showing that thrombospondin, a soluble factor released by astrocytes, induces an increase in synapse number on retinal ganglion cells by binding to the calcium channel subunit α2δ. The calcium channel subunit α2δ is also the receptor for gabapentin and pregabalin drugs currently used for the treatment of pain and epilepsy. Barres also took some time to reflect on the dearth of women in science asking everyone to view his talk on the matter of diversity in science which can be found at the following link (www.memdir.org/video/barres.html) and encouraging “students to come out as gays and women to come out as women as well.”

Human glial progenitors myelinate, move in on mouse brain

Steven Goldman MD, PhD from the University of Rochester used human glial progenitor cells from 23 week old medically necessary aborted fetal brains to treat a mouse model of myelin disease. Human progenitor cells were able to differentiate in a context dependent manner, remyelinate, and rescue the disease phenotype. Surprisingly Goldman found that over time (approximately 13 months) the human progenitor cells took over and replaced all neural cells in the mouse brain creating a humanized-mouse brain model system. This study is currently in press at Cell Stem Cell.

Small molecules push fibroblasts toward ES cell morphology

The symposium ended with Kevin Eggan PhD from Harvard University who presented his work on finding small molecule inducers of reprogramming resulting in compounds repsox and repoct. Although the combination of these two compounds could not FULLY reprogram cells, their combination did prompt fibroblast cells to form colonies resembling those of embryonic stem cells, albeit they did not express Oct4.

]]>/theniche/2009/10/notes_on_a_neural_stem_cell_co.html/feed0Ideas on stem cells: consent, use, nature/theniche/2009/10/ideas_on_stem_cells_consent_us.html
/theniche/2009/10/ideas_on_stem_cells_consent_us.html#commentsThu, 01 Oct 2009 00:50:11 +0000mbaker/theniche/2009/10/ideas-on-stem-cells-consent-use-nature.htmlRead more]]>Earlier this month, the NIH assembled a working group to decide whether currently existing human embryonic stem cell lines confirm with the spirit of guidelines released on July 7. (See Let the vetting begin ) Much of the assessment will center on informed consent procedures.

Today, Bernard Lo well-known member of that working group has correspondence in Nature regarding how informed consent should be obtained for collecting tissue for creating human induced pluripotent stem cells. In it, Lo and Bruce Conklin, both at the University of California, San Francisco call for scientists to develop basic rules that donors should agree to. Other correspondence from scholars at the University of Sydney calls for informed consent to be local.

Elsewhere, Lee Buckler of the Cell Therapy Blog laments a poll showing that many science-savvy readers (and, apparently writers at Genetic Engineering News) are unaware that adult stem cells are being tested in clinical trials.

In an interview with The Scientist, Arthur Lawler argues that researchers will not be able to home in on a single molecular network of stemness, and so the concept of cells could be more profitably pursued in the context of their own tissues rather than overarching ideas. “It’s a system level property,” Lander says, “so we need to have information about a whole system.”

For more on that see Nature Reports’ commentary, Stem cell: what’s in a name?, and our interview with Irv Weissman, in which he calls for the creation of stem cell departments. Ironically, I’m not sure anyone is fundamentally disagreeing so much as using different words to grope at similar ideas.

]]>/theniche/2009/10/ideas_on_stem_cells_consent_us.html/feed0More stem cells in Lou Gehrig’s disease/theniche/2009/09/more_stem_cells_in_lou_gehrigs.html
/theniche/2009/09/more_stem_cells_in_lou_gehrigs.html#commentsTue, 29 Sep 2009 19:51:09 +0000mbaker/theniche/2009/09/more-stem-cells-in-lou-gehrigs-disease.htmlRead more]]>Shortly after my coverage of the FDA’s approval for NeuralStem’s stem-cell trial for amyotrophic lateral sclerosis appeared on the Niche, Letizia Mazzini and Franca Fagioli of Eastern Piedmont University contacted me to tell me about their team’s work using mesenchymal stem cells for the same disease. While Neuralstem is moving forward with neural stem cells, Mazzini and colleagues have been exploring the use of mesenchymal stem cells derived from the patient who will receive them. She has recently published results of a Phase I trial as well as a review of stem-cell approaches in ALS. Unfortunately, I learned of this work only after I’d posted.

Here is their letter:

We have just read, not without some interest, the NeuralStem communicate. The trial is presented as if it were the first clinical study with stem cells in ALS (“This is the first stem-cell approach for ALS” says Lucie Bruijin). However, this needs to be rectified as we conducted two phase 1 clinical trials one in 2001 (Mazzini et al., 2008)) and the other in 2007 (Mazzini L et al., 2009). The trials were approved respectively by the regional Ethical Committee and by the Italian Institute of Health and by the and were designed to test the safety and the feasibility of mesenchymal stem cell transplantation into the spinal cord of ALS patients.

MSC were isolated from patients’ bone marrow, in vitro expanded for 3-4 passages and evaluated for quality control as requested by national rules on advanced therapies. In neither of our trials were there any immediate or delayed transplant related toxicities. Stem cells were transplanted into the spinal cord at the thoracic levels with a surgical approach. Clinical, laboratory, and radiographic evaluations of the patients showed no serious transplant related adverse events. Magnetic resonance images (MRI) showed no structural changes (including tumor formation) in either the brain or the spinal cord.

Furthermore, we also demonstrated that expanded MSCs can survive and migrate after transplantation in the lumbar spinal cord of SOD1-G93A mice, where they prevent astrogliosis and microglial activation and delay the ALS-related decrease in the number of motor neurons, resulting in an amelioration of motor performance (Vercelli A et al., 2008 ). Therefore we concluded that MSCs represent a good source of stem cells for future ALS cell based clinical trials.

Thus, the NeuralStem trial, as it appears, shows this experimental design to be no different to our studies except for the cell type: neural stem cell derived from a 8-week fetus.

]]>/theniche/2009/09/more_stem_cells_in_lou_gehrigs.html/feed088 stem cell lines submitted to NIH for ethical vetting; Harvard dominates/theniche/2009/09/88_stem_cell_lines_submitted_t.html
/theniche/2009/09/88_stem_cell_lines_submitted_t.html#commentsMon, 28 Sep 2009 18:24:17 +0000mbaker/theniche/2009/09/88-stem-cell-lines-submitted-to-nih-for-ethical-vetting-harvard-dominates.htmlRead more]]>As of 28 Sept in California, 88 human embryonic stem cell lines on a list the NIH is keeping to which institutions plan to submit which lines for an assessment of their eligibility for federal funding.

On July 7, the NIH specified strict informed consent and other criteria under which embryonic stem cell lines must be derived to be eligible for U.S. federal funding. Rather than having to meet the exact criteria of new informed consent requirements, lines derived prior to July 7 must be evaluated individually to ensure that they confirm to the principles behind the guidelines.

All but three lines are from Harvard University and its affiliated Children’s Hospital Boston; two are from Rockefeller University in New York, and one is from Children’s Memorial Hospital in Chicago. Notably absent are lines from the California universities and the University of Wisconsin. Also absent are lines derived outside the United States. However, Glyn Stacey, head of the UK Stem Cell Bank says that he believes that the guidelines on informed consent established among various groups in the UK complies with that set forward by the NIH. That was published last year in Regenerative Medicine (subscription required).

The list indicates an intent to submit rather than a formal submission, which will require substantial documentation.

]]>/theniche/2009/09/88_stem_cell_lines_submitted_t.html/feed0Stem cell vetting raises concerns, confusion/theniche/2009/09/stem_cell_vetting_raises_conce_1.html
/theniche/2009/09/stem_cell_vetting_raises_conce_1.html#commentsThu, 24 Sep 2009 12:16:23 +0000mbaker/theniche/2009/09/stem-cell-vetting-raises-concerns-confusion.htmlRead more]]>After years hearing scientists complain that the U.S. federal government funded research on too few human embryonic stem cell lines, Lana Skirboll, who directs the Office of Science Policy at the U.S. National Institutes of Health, has something to tell the stem cell community: “the ball is in their court.” The NIH announced on Monday that it would be accepting applications to determine whether a line is eligible for funding. The process is not without risks: some scientists are quietly concerned that their informed consent procedures could come under criticism, or that they could lose access to non-federal sources of funding if the lines they wish to work with aren’t cleared by the NIH.

Some confusion over the process is already evident. (See Let the vetting begin) Scientists conducting research on a hESC line should not submit it themselves, Skirboll says, but instead find out whether the group that derived the line will submit it. That’s why the draft list is public, she says. “If you see a line that you’re working on that has not been listed, you need to think about your research and talk to the deriver.”

Geoff Lomax, who heads the standards group at the California Institute of Regenerative Medicine. suspects that the evaluation process could get extremely complex, particularly for older lines. One solution, he thinks, is to assess newer lines, which should more closely follow current thinking for informed consent requirements. Setting precedents soon would be useful, he says. “There’s no need to deal with the hardest lines first.”

“I hope like heck we have so many applications that we have that problem,” says Skirboll. The first in-person meeting of the working group will not be scheduled until it’s clear that there are enough lines to evaluate. “We’re hoping that the order doesn’t matter, that we can go through them very quickly.”

Some of the usual suspects are missing from the list of human embryonic stem cell lines waiting to be evaluated by the U.S. National Institutes of Health for their eligibility federal funding. However, according to a draft list provided by the NIH, none of the hES cell lines eligible for funding under the Bush administration have been submitted, nor have any of the lines from Doug Melton’s group at Harvard. (Spokesmen for both the University of Wisconsin, where more most of the previously approved lines were derived, and the Harvard Stem Cell Institute indicated that the lines would be submitted.)

The NIH issued guidelines in July included strict criteria for documenting informed consent. (See Stem cell research expands)Lines created after this date will undergo a simple administrative review for strict compliance with the guidelines. But the more-studied lines derived prior to the guidelines will need to be evaluated one-by-one by an NIH working group to see if they are consistent in spirit with the guidelines. Though lines that do not pass muster with the NIH can still receive research funding from private organizations and individual states, the deliberations of the NIH working group will be made public, these granting agencies may prove reluctant to award funds to material lacking such approval.

Moreover, the evaluation will require universities to submit sensitive material. Any documentation containing personally identifiable information about donors will not be retained by NIH, says Skirboll, and though consent forms and other documentation will not be made public, she says, it will be subject to the Freedom of Information Act..

Institutions have legitimate worries about public overreaction and the disclosure of proprietary information, says Robert Streiffer, a bioethicist at the University of Wisconsin, has raised concerns about the informed consent standards applied to funding hESC lines under the Bush administration. (See When the past catches up with the present.) Nonetheless, he says, “If you’re not willing to publicly disclose the conditions under which you derived your cells, that’s a pretty big red flag”.

With the exception of two lines from biotech company Bresagen, Streiffer thinks lines eligible for funding under President Bush will also be deemed eligible for funding under the Obama administration.

The more interesting question, Streiffer says, is whether the NIH will seek to enforce consent criteria unique to particular lines. For example, he says, hES cells cannot be mixed into human embryos under the Obama guidelines, but consent forms from the University of Wisconsin state that cells cannot be mixed with any sort of embryo.

Skirboll says that specific consent conditions will be posted along with the lists of lines eligible for federal funding, and that grant applications proposing experiments outside these conditions will not be eligible for funding.